For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at .

The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.

The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom.

Library of Congress Cataloging-in-Publication Data

A catalogue record for this book is available from the British Library.

ISBN: 9780470711187

Dedication

As you set out for Ithaca
hope your road is a long one,
full of adventure, full of discovery.
Laistrygonians, Cyclops,
angry Poseidon – don’t be afraid of them:
you’ll never find things like that on your way
as long as you keep your thoughts raised high,
as long as a rare excitement
stirs your spirit and your body.

ITHACA (Konstantinos Kavafis, 1911)

This book is dedicated to my wonderful wife Eleni-Angeliki and my lovely son George-Alexander and daughter Eugenia-Erene. I thank them for their continuous support and patience.

Hot-melt Extrusion (HME) is an emerging continuous processing technology for the development of various solid dosage forms and drug delivery systems. In the last 20 years HME has attracted increased attention from both the pharmaceutical industry and academia. The enormous need for new dynamic manufacturing processes to produce robust finished products makes HME an excellent technology. Although there are several publications on HME applications, this is the first attempt to provide a concrete overview of HME pharmaceutical applications.

The aim of this book is to present a comprehensive review of the theory, instrumentation and wide spectrum of applications. The book is targeted at scientists in academia and industry and graduate students in various research-intensive programs in pharmaceutical sciences and medicine who are dealing with many aspects of drug formulation and delivery, pharmaceutical engineering and processing and polymers and materials science.

Chapters 1 and 2 discuss single- and twin-screw extrusion operational principles, design and critical processing parameters. Chapter 3 is an overview of HME developments in pharmaceutics, and discusses a number of drug delivery systems and physicochemical characterization techniques of HME extrudates. Chapters 4 and 5 deal with theoretical approaches of drug–polymer miscibility estimation and discuss the role, influence and selection of plasticizers in the HME process. Chapters 6 and 7 provide in-depth knowledge of drug products extruded by a wide range of polymers and their applications. More detail is provided in Chapter 8 where the application of HME for the manufacture of thin films is discussed. Chapter 9 is dedicated to the employment of HME for the taste-masking of bitter APIs, and discusses the selection of various excipients for these purposes.

Chapter 10 includes a comprehensive discussion of clinical studies performed by various groups, bioavailability and pharmacokinetics of oral immediate release, oral controlled release and implants. The relatively new manufacturing process of injection molding is introduced in Chapter 11, and aspects such as critical process parameters, excipients, new products and their properties are critically analyzed. A comprehensive discussion of dispersive and distributive mixing is included in Chapter 12 and case studies are presented.

The reader can find important information in Chapter 13 about the scale-up of the hot-melt extrusion process from a lab-scale extruder to a commercial-scale extruder, as well as different scale-up scenarios. Novel applications of HME for the manufacturing of devices and implant systems can be found in Chapter 14, including examples of marketed products.

Chapter 15 is an FDA perspective on HME product and process understanding with special attention given to Quality by Design (QbD) as a tool to understanding HME processing. Finally, Chapter 16 introduces a process analytical technology (PAT) approach by using near-infrared spectroscopy for understanding and controlling the hot-melt extrusion process in the pharmaceutical industry.

I would like to acknowledge the valuable support and cooperation of all the contributing authors throughout this process, to whom I offer a most sincere thank you. Without their dedication and timely submission of material, this book would not have been published.